Chronic kidney disease is a major cause of morbidity and mortality affecting 10-20% of the world population, with glomerulonephritis accounting for a significant proportion of cases1-3. IgA nephropathy (IgAN) is the most common form of glomerulonephritis and the most common cause of kidney failure among Asian populations2,4. The diagnosis of IgAN requires documentation by kidney biopsy demonstrating proliferation of the glomerular mesangium with deposition of immune complexes predominantly composed of Immunoglobulin A (IgA) and complement C3 proteins3,5,6. Registry data as well as autopsy and kidney-donor biopsy series suggest that there is a significant variation in prevalence among different ethnicities: IgAN is most frequent among Asians, with a disease prevalence as high as 3.7% detected among Japanese kidney donors, but is rare among individuals of African ancestry5 and of intermediate prevalence among Europeans (up to 1.3%)6.
The pathogenesis of IgAN is uncertain8,9. The finding of IgA1 glycosylation abnormalities among European, Asian, and African-American populations has suggested a shared pathogenesis among different groups10-15. Moreover, familial aggregation of IgAN has been reported among all ethnicities, suggesting a genetic component to disease8,16. To date linkage studies have identified several loci predisposing to IgAN, but underlying genes are not known8,16-18. A single, unreplicated genome-wide association study (GWAS) in a small European cohort (533 cases) has reported association of IgAN with the MHC complex19.
Identifying specific mutations in one or more genes could be used as the basis for a noninvasive method to diagnose a predisposition to IgAN, and deciding which indications merit undergoing renal biopsy and prophylactic treatment.